Olfactory neurons are an excellent model cell type for understanding signal transduction pathways and their regulation in vivo. Because of its simple nervous system and powerful genetics, the nematode C. elegans provides an opportunity to understand olfaction at the level of behaviors, neurons, genes and molecules. Individual C. elegans olfactory neurons express multiple olfactory receptor genes and detect multiple odorants that can be discriminated by the animal. To begin to ask how different stimuli are distinguished within one cell, the receptor genes that are expressed within one olfactory neuron will be defined. Receptors in the AWA olfactory neurons will be sought based on their regulation by the AWA-specific transcription factor, odr-7. As a further tool for understanding sensory discrimination, the odorant ligands for these receptors will be determined using in vivo functional assays. Expression of some olfactory receptor genes is regulated by the animal's experience, suggesting that neurons use transcriptional mechanisms to regulate the flow of sensory information. To understand these regulatory pathways, the AWA receptor genes will be examined for their regulation by neuronal activity and by experience. OSM-9 is the first molecule in a novel C. elegans sensory signaling pathway that is also used in mammalian pain-sensing neurons. A suppressor screen in an osm-9 mutant background has led to the identification of 41 new mutations that suppress the osm-9 defect. These mutations will be characterized and genes that interact with osm-9 will be cloned to gain more insight into this conserved sensory signaling pathway. Management of acute and chronic pain is one of the central issues in cancer treatment as well as other disease states, and the new genes from this screen are potential targets for therapeutic intervention in pain syndromes.